Intratumor heterogeneity has been widely reported in human cancers, but our knowledge of how this genetic diversity emerges over time remains limited. A central challenge in studying tumor evolution is the difficulty in collecting longitudinal samples from cancer patients. Consequently, most studies have inferred tumor evolution from single time-point samples, providing very indirect information. These data have led to several competing models of tumor evolution: linear, branching, neutral and punctuated. Each model makes different assumptions regarding the timing of mutations and selection of clones, and therefore has different implications for the diagnosis and therapeutic treatment of cancer patients. Furthermore, emerging evidence suggests that models may change during tumor progression or operate concurrently for different classes of mutations. Finally, we discuss data that supports the theory that most human tumors evolve from a single cell in the normal tissue. This article is part of a Special Issue entitled: Evolutionary principles - heterogeneity in cancer?, edited by Dr. Robert A. Gatenby.

中文翻译：

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肿瘤演变：线性，分支，中性或点状？

肿瘤内异质性已在人类癌症中广泛报道，但我们对这种遗传多样性如何随时间出现的知识仍然有限。研究肿瘤演变的一个主要挑战是难以从癌症患者那里收集纵向样本。因此，大多数研究都从单个时间点样本推断出肿瘤的发展，从而提供了非常间接的信息。这些数据导致了几种竞争性的肿瘤进化模型：线性，分支，中性和标点。每个模型对突变的时间和克隆的选择做出不同的假设，因此对癌症患者的诊断和治疗具有不同的含义。此外，新兴证据表明，模型可能会在肿瘤进展过程中发生变化，或针对不同类别的突变同时运行。最后，我们讨论了支持大多数人类肿瘤从正常组织中的单个细胞演变而来的理论的数据。本文是由Robert A. Gatenby博士编辑的题为：进化原理-癌症的异质性？的特刊的一部分。